Amphotericin B toxicity in VL — DTM&H MCQ

Correct answer: B — Switch to liposomal amphotericin B

The correct answer is B, switch to liposomal amphotericin B. This patient has developed acute nephrotoxicity (creatinine more than doubled from 90 to 220 umol/L) plus infusion rigors on conventional amphotericin B deoxycholate, a well recognised and dose-limiting toxicity of this formulation in visceral leishmaniasis (VL) treatment in the Indian subcontinent. Liposomal amphotericin B has much lower rates of nephrotoxicity and infusion reactions because the lipid encapsulation reduces free drug binding to renal tubular cell membranes, and it is the preferred agent for VL in South Asia, including single-dose regimens used successfully in Bihar and Bangladesh. Continuing or slowing conventional amphotericin risks further, potentially irreversible, renal injury, so the correct step is to switch formulation rather than persist with deoxycholate. Trial data confirm liposomal amphotericin B causes far less renal toxicity than the deoxycholate formulation while retaining efficacy, supporting the switch as the safest evidence based option. Why the other options are wrong: E. Continue with slower infusion rate: slowing the infusion may reduce rigors slightly but does nothing to address established nephrotoxicity, which is due to direct tubular and vascular toxicity of the deoxycholate vehicle, not infusion speed alone; continuing the same drug risks further renal deterioration. D. Switch to miltefosine orally: miltefosine requires a full 28 day course from the start for efficacy and is teratogenic, making it unsuitable as a rescue switch mid-treatment and inappropriate without confirming the patient is not of childbearing potential or pregnant. C. Add N-acetylcysteine for renal protection: there is no established evidence base or guideline recommendation for N-acetylcysteine in amphotericin-induced nephrotoxicity, and it does not remove the ongoing nephrotoxic insult from continued deoxycholate exposure. A. Stop all treatment and observe: VL is fatal if untreated, so stopping treatment entirely and merely observing abandons definitive antileishmanial therapy rather than substituting a less nephrotoxic agent. Key point: Rising creatinine with rigors on amphotericin B deoxycholate should prompt switching to liposomal amphotericin B, which retains efficacy against Leishmania donovani with substantially lower nephrotoxicity.

Reference: The Lancet Global Health, Mondal et al, Single-dose liposomal amphotericin B: an effective treatment for visceral leishmaniasis (2013), and NEJM Sundar et al, Single-Dose Liposomal Amphotericin B for Visceral Leishmaniasis in India (2010), https://www.nejm.org/doi/full/10.1056/NEJMoa0903627